Earlyonset epileptic encephalopathies eoees are neurological disorders in children characterized by frequent severe seizures and persistent abnormality of cortical. All demonstrate reduced brain volume with bilateral, severe pachygyrialissencephaly. Znhit3 is defective in peho syndrome, a severe encephalopathy. The phenotypic and molecular spectrum of peho syndrome and.
Increased plasma malondialdehyde associated with cerebellar. This complex is nonspecific, but within this syndrome, a subgroup with a defined neuropathologic phenotype and apparently autosomal recessive inheritance exists. Two of the autopsied patients were sisters and two other cases were familial. The term peho like syndrome has been proposed for patients who share clinical features of peho syndrome but lack the cerebellar atrophy, one of its major diagnostic criteria. Uniform neuropathological changes are described in eight cases of the progressive encephalopathy syndrome with edema, hypsarrhythmia and optic atrophy peho syndrome. Clinical features of peho syndrome caused by ccdc88a truncating mutation.
Serial mr imaging, diffusion tensor imaging, and mr. They showed profound generalized hypotonia early in infancy and developed infantile spasms with hypsarrhythmia within the first. Ccdc88a mutations cause peholike syndrome in humans and. At birth he had weak cry, microcephaly head circumference 31 cm, jan 01, 2007 a significant number of patients have been described who displayed most of the diagnostic criteria and features of peho syndrome, but did not appear to have cerebral atrophy on mri, lacked the ophthalmologic signs and showed no reduction in csf igf1 levels. Browse az genetic and rare diseases information center. Oligohydramnios was detected in the last trimester of pregnancy. Geoffrey woods1 these authors contributed equally to this work.
Pdf serial mri in a child with peho syndrome hakan. Autosomalrecessive variations of ap3b1, the ubiquitous isoform, cause hermanskypudlak syndrome type 2. Patients and consumers with specific questions about a genetic test should contact a. Somer 1993 indicated that cerebellar hypoplasia is a cardinal diagnostic feature of peho syndrome and suggested that a peholike syndrome the same clinical manifestations with only mild supratentorial atrophy may occur. Peho syndrome is a rare progressive infantile encephalopathy with onset within the first few months of life. Progressive encephalopathy with edema, hypsarrhythmia and optic atrophy peho syndrome is a distinct neurodevelopmental disorder. Retinal and optic nerve changes in microcephaly neurology. They describe a novel finding, precocious puberty, a feature not previously reported in this syndrome. Mar 17, 2020 the authors discuss a child with peho like syndrome and underline the need for a careful followup of these patients to identify signs and symptoms that can have a later onset, such as optic atrophy. This is a standard security test that we use to prevent spammers from sending automated requests. The molecular bases of both clinically defined conditions remain unknown in spite of the. The endpoint of different genetic epilepsies background progressive encephalopathy, hypsarrhythmia and optic atrophy peho has been described as a.
Peho syndrome is enriched in the finnish population with an estimated incidence of 1. The peho syndrome progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy is a recently recognised disorder of unknown biochemical background. We describe two familial and three nonfamilial cases from argentina, examined between february 1, 1990july 31, 2008, who met the diagnostic criteria of progressive encephalopathy, peripheral edema, hypsarrhythmia, and optic atrophy syndrome. No metabolic cause of progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy peho syndrome or peholike patients has been found. Jan 15, 2003 peho syndrome is a rare progressive infantile encephalopathy with onset within the first few months of life. Cranial magnetic resonance imaging mistakenly suggests prenatal ischaemia in peholike syndrome ncbi. Somers distinction between classical peho and peholike syndromes has been questioned3, 4. Background progressive encephalopathy, hypsarrhythmia and optic atrophy peho has been described as a clinically distinct syndrome.
Diagnostic criteria and genetics of the peho syndrome. The role of neurofilament aggregation in neurodegeneration. The distinct clinical criteria for the peho syndrome are infantile hypotonia. Low highdensity cholesterol in patients with progressive. Cranial magnetic resonance imaging mistakenly suggests prenatal ischaemia in peho like syndrome ncbi. Peho syndrome progressive encephalopathy with edema. The endpoint of different genetic epilepsies background progressive encephalopathy, hypsarrhythmia and optic atrophy peho has been described as a clinically. Method measurements of mda concentrations in plasma were compared among healthy children n31, patients with neurological disorders or epileptic syndromes n15, and children with pontocerebellar structural defects n31, where the. The inclusion criteria were based on the information received from the original peho cases table 1. He was born at term by normal delivery birthweight 2.
They suggested that the disorder may be more frequent than would be suggested based on the original diagnostic criteria. Autosomalrecessive mutations in ap3b2, adaptorrelated. Progressive encephalopathy with edema, hypsarrhythmia, and. Pdf the phenotypic and molecular spectrum of peho syndrome. Peho syndrome is a rare symptom complex of severe p rogressive encephalopathy, e dema, h ypsarrhythmia, and o ptic atrophy.
Nfs belong to the family of cytoskeletal intermediate. Peho syndrome genetic and rare diseases information. The levels of igf1 in the patients with peho syndrome were significantly lower than in the controls and in the peho like syndrome. Few patients fulfilling the diagnostic criteria for peho syndrome have been reported outside finland. Report ccdc88a mutations cause peho like syndrome in humans and mouse michael s. The molecular bases of both clinically defined conditions remain unknown in spite of the widespread application of. Microcephaly is a clinical finding, not a disease, and is a crude but trusted assessment of intracranial brain volume. The relative frequency among the epileptic syndromes is an another reason why not only neuropediatricians but also general pediatricians must be fully informed about diagnostic, clinical, imaging and genetic. Clinical features help list of clinical features of the conditionphenotype displayed from sources such as the human phenotype ontology hpo and omim.
Peho syndrome the end point of severe epilepsies european. However, the aetiology is poorly understood, and the genetic basis of the condition has not been fully elucidated. Our objective was to discover if peho syndrome is a single gene disorder. Many neurodegenerative disorders, including parkinsons, alzheimers, and amyotrophic lateral sclerosis, are well known to involve the accumulation of diseasespecific proteins.
The authors discuss a child with peholike syndrome and underline the need for a careful followup of these patients to identify signs and symptoms that can have a later onset, such as optic atrophy. Method measurements of mda concentrations in plasma were compared among healthy children n31, patients with neurological disorders or epileptic syndromes n15, and children with pontocerebellar structural defects n31, where the cause or genetic defect remained unknown. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126. The phenotypic and molecular spectrum of peho syndrome and peholike. It is a very rare disease, one of the finnish heritage diseases, although approximately half of the cases reported so far are notfinnish and have been described worldwide. Peho syndrome is very rare in other populations with syndrome. Peho syndrome is a pediatric disorder of unknown origin, characterized by a combination of postnatally progressive encephalopathy. The peho syndrome progressive encephalopathy with oedema. We report on two japanese siblings one female and one male with peho syndrome progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy. However, no single gene has been identified as causative1, 5 and an autosomal dominant form. Report ccdc88a mutations cause peholike syndrome in. Less well known are the accumulations of another set of proteins, neuronal intermediate filaments nfs, which have been observed in these diseases for decades.
Peho syndrome may represent phenotypic expansion at the. The current case report presents and discusses serial conventional mr imaging findings and serial functional studies including diffusion tensor imaging and quantitative mr spectroscopy. This group of patients was diagnosed with peholike syndrome. Peho syndrome is a progressive encephalopathy with edema, hypsarrhythmia and optic atrophy. The term peholike syndrome has been proposed for patients who share clinical features of peho syndrome but lack the cerebellar atrophy, one of its major diagnostic criteria. It has been postulated that it is an autosomal recessive condition. A 6monthold boy born to nonconsanguineous parents presented with intractable seizures from the fourth month of age. No metabolic cause of progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy peho syndrome or peho like patients has been found. Diagnostic features have been found in neuroradiological and neuropathological studies, which show characteristic severe cerebellar atrophy. This group of patients was diagnosed with peho like syndrome. Freeware quantum resonance magnetic analyzer free downloads.
The goal of this study was to assess the serum lipid pattern of the patients. Although peho could be considered a very rare syndrome, it has been reported. Investigating microcephaly archives of disease in childhood. Ser31leu mutation in the znhit3 gene causing peho progressive encephalopathy. Sainioepilepsy and the electroencephalogram in progressive encephalopathy with edema, hypsarrhythmia and optic atrophy the peho syndrome. The relative frequency among the epileptic syndromes is an another reason why not only neuropediatricians but also general pediatricians must be fully informed about diagnostic, clinical, imaging and genetic aspects. Report ccdc88a mutations cause peholike syndrome in humans. Autosomalrecessive mutations in ap3d1 cause a severe disorder cumulating the symptoms of the ap3b1 and ap3b2 defects. Background malondialdehyde mda in plasma is regarded as an indicator for increased lipid peroxidation. The peho syndrome progressive encephalopathy with oedema, hypsarrhythmia and optic atrophy is an early onset neurodegenerative disorder presenting with infantile spasms, profound psychomotor.
Peho syndrome is very rare in other populations with download pdf. Pdf download buy article permissions and reprints abstract we report on two japanese siblings one female and one male with peho syndrome progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy. My daughter virginie has peho syndrome peho progressive encephalopathy with edema, hypsarrhythmia and optic atrophy. The current case report presents and discusses serial conventional mr imaging findings and serial functional studies including diffusion tensor imaging and quantitative mr spectroscopy findings in a 6yearold child with peho. Methods this was a prospective casecontrol study including 27 patients with microcephaly and 27 healthy controls. For language access assistance, contact the ncats public information officer. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for peho syndrome. Defective production of igf1 probably reflects the underlying neurodegeneration and the increase in no production probably reflects the seizure activity andor neurodegeneration. Nih does not independently verify information submitted to the gtr. Developmental processes reducing in utero neuron generation present at birth with primary microcephaly. A significant number of patients have been described who displayed most of the diagnostic criteria and features of peho syndrome, but did not appear to have cerebral atrophy on mri, lacked the ophthalmologic signs and showed no reduction in csf igf1 levels.
Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree. Nih makes no endorsements of tests or laboratories listed in the gtr. If you have problems viewing pdf files, download the latest version of adobe reader. Report ccdc88a mutations cause peholike syndrome in humans and mouse michael s. Methods brain ct or mr studies were performed on 21 patients with.
In patients with the peho syndrome, as compared with controls, the levels of igf1 were reduced and the levels of nitritenitrate were markedly elevated. This study included 8 patients with peho syndrome aged 6. Peho syndrome genetic and rare diseases information center. Nahorski,1, masato asai,2, emma wakeling,3 alasdair parker,4 naoya asai,2 natalie canham,3 susan e. Affected infants have facial dysmorphism and suffer from severe hypotonia, profound mental retardation, convulsions often with a hypsarrhythmic eeg pattern.
It is postulated to be an autosomal recessive condition. Secondary microcephaly develops after birth and predominantly reflects dendritic or white matter diseases. The peho syndrome is a rare symptom complex of severe progressive. The infantile spasms are refractory to antiepileptic drugs or adrenocorticotropic hormone acth therapy. However, no single gene has been identified as causative1, 5 and an autosomal dominant form of peho syndrome has also been described. It is a very rare disease, one of the finnish heritage diseases, although approximately half of the cases reported so far are notfinnish and have been described worldwide it has been suggested that it may also be present in australian and american populations. Patients without optic nerve atrophy and brain imaging abnormalities but fulfilling other peho criteria are often described as a peholike syndrome. All five children were products of normal gestation, although one was premature. The levels of igf1 in the patients with peho syndrome were significantly lower than in the controls and in the peholike syndrome. In combined neuroradiological and ophthalmological studies, 10 out of 21 possible peho. Objective to investigate the morphology of the retina and optic nerve on in microcephaly. This epileptic disorder has become a classic topic for neuropediatricians and the interest is documented by the large number of publications on this subject. For more information about the disease, please go to the disease information page.
682 44 1567 104 404 910 1128 966 64 1412 22 27 1221 553 344 16 1385 636 475 986 1290 739 1046 598 452 484 926 1365 636 836 1260 973 979 815 1078